Organ transplantation is currently performed as the main therapy for irreversible organ dysfunction due to illnesses or accidents. Although the number of transplantation cases have increased and the success rates thereof have dynamically risen by advances in immunosuppressing agents or transplantation technologies, chronic organ shortages are posing a serious problem in transplantation medical care (Non-Patent Literature 1). Even though a method for transplanting a transplant animal organ or a development of gene-modified animals with less tendency to cause immunological rejection (Non-Patent Literatures 2 and 3), and further a development of artificial organs aiming to replace organ functions with artificial materials have been promoted in order to accommodate for this organ shortage (Non-Patent Literature 4), none of the technology developments have reached a point of replacing adult organ function.
The shortage of donor organs provided for transplantation is not only because of the number of organs provided, but the short duration that the isolated organ can be preserved in a transplantable state is also one great reason. For this reason, development of a technology for preserving the isolated organ ex vivo for a long-term in a transplantable state has been promoted. The method currently most broadly employed is a simple cooling method of replacing the blood in the organ with a low-temperature organ preservation solution and then immersing in a low-temperature preservation solution to suppress cell metabolism. There is also a perfusion cooling preservation method that perfuses the vascular plexus in the organ with a low-temperature organ preservation solution while performing immersion preservation at a low temperate in order to remove waste products in the organ in preservation, which is recently under trial in Europe and the U.S. (Non-Patent Literature 5).
However, safe expiration time of organs preserved by these methods is thought to be 60 hours for kidneys and 20 hours for livers in general, and an elongation technology for further duration of preservation has been desired.
Moreover, in addition to the above problems, another factor causing the shortage in the number of donor organs is that organs that can be provided are limited because the majority of donor registrants die of cardiac arrest. In organ transplantation from cardiac arrest donors, in contrast to organ transplantation from brain-dead donors, a period during which the blood flow to organs is stopped, in other words a period of “warm ischemia” occurs between cardiac arrest and isolation and preservation of organs. Cell swelling disorder the to depletion of ATP or accumulation of waste products such as hypoxanthine are caused in an organ or tissue in warm ischemic state. The hypoxanthine accumulated in cells is rapidly metabolized by the oxygenated perfusate when blood flow to the organ or tissue is resumed. During this process, tissue disorder may be provoked by the large amount of reactive oxygen produced, and systemic acute shock may be evoked in the recipient receiving the organ transplantation by cytokines etc. secreted from cells.
Because an organ or tissue becomes maladaptive for organ transplantation when warm ischemic state is continued for a few minutes due to organ or tissue disorder accompanying warm ischemia and reperfusion, the transplantation adaptation rate of organs from donors who have died from unexpected cardiac arrests outside hospitals is currently only 10% or less, and further the transplantation engraftment rate therefrom remains at about 70%. (Non-Patent Literature 6)
In other words, the transplantation adaptation rate of organs from cardiac arrest donors remain at a very low level compared to the transplantation adaptation rate of organs from brain-dead donors, and development of a technology that enables organ donation from cardiac arrest donors is desired in order to expand the number of donor organs.